Aim To investigate the protective effects of silymarin on cardiac muscle in diabetic rats and explore its therapeutic mechanism. Methods The SD rats were randomly divided into five groups: the normal control group,the diabetic model group,the low,middle,high doses of silymarin therapy group.The diabetic model was established following intraperitoneal injection of streptozocin with 60 mg/kg.Silymarin of 50,100,200 mg/kg was given to the low,middle,high doses of drug therapy group for 12 weeks.Fasting blood glucose,serum fructosamine and heart function were respectively measured.Semiquantitative expressions of transforming growing factor-β1(TGF-β1),matrix metalloproteinases-9(MMP-9) and tissue inhibitors of matrix metalloproteinase-1(TIMP-1) protein were determined by immunohistochemistry and Western Blotting. Results Compared with the normal control group,fasting blood glucose,serum fructosamine of the diabetic rats were significantly upregulated(P><0.01).Left ventricular end diastolic pressure(LVEDP) were much higher(P><0.01),and left ventricular systolic pressure(LVSP),±dp/dtmax were declined significantly(P><0.01) by heart function measured.The protein expression of TGF-β1,MMP-9,TIMP-1 and MMP-9/TIMP-1 were significantly upregulated(P><0.01).Compared with the diabetic group,fasting blood glucose and serum fructosamine of silymarin therapy groups were significantly decreased(P><0.01).LVEDP were significantly declined(P><0.01),and LVSP,±dp/dtmax were elevated(P><0.01) by heart function measured.The protein expression of TGF-β1,MMP-9,TIMP-1 and MMP-9/TIMP-1were significantly decreased(P><0.01). Conclusion The expression of TGF-β1,MMP-9,TIMP-1 are related to diabetic cardiomyopathy(DCM),Silymarin has protective effect on DCM through affecting the changes of indexes mentioned above.